In germfree animals during the past decade, deviations from normality have been observed in a variety of details which could not be readily attributed to the absence of the normal microbial flora. These anomalies, some indicating a profound involvement of the germfree host, have presented potential sources of error in the use of these animals as research tools. The objective of this proposal is to seek remedial steps for eliminating these germfree anomalies while still maintaining the germfree state of the animal. The goals set for the current year include the following: (a) Elaboration of experimental models for association of germfree animals with synergistic flora elements and testing for concomitant shifts in these animals' anomalous characteristics. (b) Exploration of reproducible and possibly simple bioassay procedures in this largely untested area. (c) Establishment of laboratory facilities and routines needed for these purposes.